The heart must adapt to continually varying demands, often more quickly than external control can compensate. Thus, there must be some intrinsic regulation of cardiac pumping. Although isolated cardiac muscle studies show that contractility varies from beat-to-beat, these short-term adaptations are not well understood. I have described a phenomenon whereby cardiac function on any beat is influenced by the ejection and systolic load of the previous beat. I hypothesize that this previous beat contraction history is very important in beat-to-beat regulation of contractility. Further, I hypothesize that myocyte calcium and contractile protein kinetics a re structured so that the mechanics of contraction of one beat influence the activation state, and thus contraction, of the next beat. The specific aims of this proposal are: 1. To quantify the roles of pervious beat ejection, ejection timing, and systolic load in determining left ventricular function. 2. To determine the time course of previous beat contraction history. 3. To determine the influence of inotropic state on the expression and strength of previous beat contraction history. 4. To identify the underlying cellular bases of previous beat contraction history. I propose both isolated heat experiments in which left ventricular function is evaluated under precisely controlled contraction histories and theoretical mathematical modelling of left ventricular function based on calcium and contractile protein kinetics. The resulting quantitative descriptions of previous beat ejection and loading in determining left ventricular function will increase our knowledge of beat-to-beat regulation of cardiac pumping and will enhance the assessment of cardiac function. These studies will also increase our knowledge of the cellular mechanisms that regulate excitation- contraction coupling.